Presenting the results at the Experimental Biology conference in
Boston, the company explained that although we're still a long way
off bioprinting a complex transplantable human liver, creating a
tiny model in the lab could be key in tackling liver diseases.

"We believe these models will prove superior in their ability to
provide predictive data for drug discovery and development, better
than animal models or current cell models," Keith Murphy, CEO of
San Diegio based Organovo, said in a statement.

Liver cells, such as parenchymal hepatocytes, are routinely used
in testing the harmful or beneficial affects of drugs in the lab.
However, flat 2D models are not representative of a real human
liver, lacking many of the functions and complex cell networks that
would alter the drugs' efficacy. Creating a better model, could
dramatically speed up research.

Organovo's technique -- first spotted by New Scientist and deemed "highly
reproducible" by its creators -- uses its NovaGen bioprinter and a
support gel to print 20 layers of liver cells (from donated livers
or surgical waste) into a petri dish. It used hepatocytes cells --
which make up about 80 percent of a liver's mass and enable most
functions, from protein storage to carbohydrate conversion -- with
endothelial and hepatic stellate cells arranged in
between. Endothelial cells form the lining of blood
vessels, and so the early formation of microvascular networks
occurred in the tiny lab liver. This ensured
nutrients and oxygen could be delivered throughout the tissue,
which is why it is able to survive for five and a
half days in the lab outside of the body.

The actual technique is also key -- cells are dropped onto
the dish individually to form a honeycomb pattern, which meant the
ratio between hepatocyte and the other cells could be managed. It
creates a tight mesh-like network of cells that, as it matures,
begins to mirror the same formation and cell density of a real
liver inside the body.

The liver is incredibly tiny -- just half a millimetre thick and
four millimetres wide. Yet this minute organ, with little visual
resemblance to the real thing in its petri dish home, manages to
replicate key processes done by the real thing. It produced the
protein albumin and synthesised plasma glycoproteins fibrinogen and
transferrin. These are all vital in getting nutrients, hormones and
drugs to the blood and the rest of the body. It also generated
fat-carrying cholesterol. For its detoxification functions, the
liver also needs to produce certain enzymes including CYP 1A2 and
CYP 3A4 -- which this tiny organ precursor also did. Its albumin
production was between five and nine times more than in 2D flat
cell structures engineered.

" I do believe we will see implantable liver tissue in
my lifetime"

Sharon Presnell, CTO, Organovo

"The current [2D] model is so inadequate, and just getting
halfway to perfection is so useful that we can refine it over
time," Murphy told Xconomy. "Not only can these tissues be a first step towards a
larger 3D liver, laboratory tests with these samples have the
potential to be game changing for medical research."

Organovo's main goal is in generating better human tissue in the
lab for disease modelling and drug discovery, and although its main
focus is not in creating whole complex organs, CTO Sharon Presnell
commented: "I'm not saying I'm going to give you an entire
liver in a box, but I do believe we will see implantable liver
tissue in my lifetime."

According to a report by KPBS, the company plans to sell the liver tissue to drug
researchers by 2014.

In the meantime, the company will be looking to increase the
life span and size of the tissue samples, which could be down to
ensuring better nutrient and oxygen delivery. This was the focus of
a University of Pennsylvania study covered by Wired.co.uk in July 2012, when bioengineers developed a
technique for 3D printing vascular structures using sugar and a
degradable polymer derived from corn. Cells could be grown around
the 3D printed structure, after which it would dissolve to leave
hollow vessels intact. Nutrients and oxygen could be delivered
throughout the network, with blood vessel cells then introduced to
extend the maze further. When the team trialled the technique using
liver cells, survival rates increased and functionality
improved.